Overview of Endocrine System Endocrine glands secrete into
extracellular space, secretion (hormones) diffuses to circulatory
system Includes primary glands - pituitary, thyroid, parathyroid,
adrenal, & pineal glands Accessory structures with glandular
function as well as others - hypothalamus, thymus, pancreas,
ovaries, testes, kidneys, small intestine heart & placenta (and
others)
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More Overview Provides homeostasis control along with nervous
system Hormonal control usually slower and longer lasting -
dependent on blood supply and receptors Control metabolism, growth
& development and reproduction In some cases the two interact
together May stimulate or inhibit the other, or modulate the effect
of the other (smooth & cardiac muscle, some glands ) Some
neurotransmitters are also hormones
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Hormonal Chemistry Lipid soluble vs. water soluble hormones
Lipid soluble - steroids, T 3 & T 4 thyroid hormones, nitric
oxide Water soluble - amines, peptides/proteins, eicosanoids May be
circulating or local hormones Local may be paracrines or autocrines
and are typically short-lived Circulating typically destroyed by
liver and excreted by kidney
Slide 5
More Hormonal Chemistry Steroids (lipid) - derived from
cholesterol, differences in side chains of 4-ring structure
Secretory cells derived from mesoderm Produced by adrenal cortex,
kidneys, testes/ovaries Thyroid hormones - combination of two
molecules of tyrosine bound to iodine Produced by thyroid
gland
Slide 6
Even More Chemistry Amines - derived from amino acids
Catecholamines (epi, norepi & dopamine) - derived from tyrosine
Histamine - derived from histidine Serotonin & melatonin - from
tryptophan Produced by adrenal medulla, mast cells, platelets
(serotonin), pineal Peptides/proteins - 3-200 amino acids, some are
glycoproteins (e.g. TSH) Produced by hypothalamus, ant. pituitary,
pancreas, parathyroids, thyroid, stomach, & small intestine,
kidneys and adipose tissue
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Still More Hormonal Chemistry Eicosanoids - derived from
arachidonic acid (20-C fatty acid) including prostaglandins and
leukotrines Primary local activity Produced by most cells (except
RBCs)
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Hormone Transport Water-soluble free in blood Lipid-soluble
largely attached to transport proteins except for a small free
fraction (0.1-10%) Transport proteins produced in liver When
attached to transport protein, hormone is less likely to leave CV
system (including loss in kidney)
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Hormonal Effects Effects include synthesis of new molecules,
changed membrane permeability, stimulated transport of molecules
across cell membrane, rate of metabolic reactions, contraction of
smooth or cardiac muscle Effect dependent on target cell - those
cells with receptors for hormone Effect may change depending on
target cells - e.g. insulin synthesis of glycogen in liver cells or
triglycerides in adipose cells
Slide 10
More Hormonal Effects Some receptors on cell membrane - water
soluble hormones (catecholamines & peptide/proteins) Some
receptors inside cells - lipid soluble hormones (steroids &
thyroid hormones) Solubility determines how hormonal drugs are
given - e.g. insulin is water soluble and must be injected
Slide 11
Even More Hormonal Effects Number of receptors changes -
altered level of response Excess hormone level - down-regulation
Deficient hormone level - up-regulation Interactions between
hormones may be related to up or down-regulation
Slide 12
Action of Lipid-soluble Hormones Interact with receptors in
cytosol or nucleus Activated receptor activates or inactivates
genetic expression Changed genetic expression, alters protein
manufacture (usually an enzyme) and ultimately cells activity
related to protein
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Action of Water-soluble Hormones Interact with surface
receptors (first messenger) Activated external receptor initiates
second messenger Frequently cAMP - formed from ATP by adenylate
cyclase (activated by G-proteins in cell membrane) Activity of
second messenger dependent on target cell cAMP stimulates break
down of triglycerides in adipose cells while increasing secretion
of thyroid hormone in thyroid cells
Slide 14
More Action of Water-soluble Hormones cAMP activates protein
kinase phosphorylates target cell enzymes which activates or
inactivates enzyme altered cell activity (regulation of other
enzymes, secretion, protein synthesis, membrane permeability)
Phosphodiesterase ultimately inactivates cAMP Some hormones
decrease cAMP Other secondary messengers include Ca 2+, cGMP,
inositol triphosphate (IP 3 ), and diacylglycerol (DAG)
Slide 15
Other Hormone Action Enzymatic amplification of hormones single
hormone molecule multiple G- proteins activated adenylate cyclase
multiple cAMP Hormonal interactions Permissive effect - activity of
some hormones requires recent or simultaneous presence of another
hormone (e.g. thyroid hormones and cortisol support action of other
hormones) via up-regulation or required presence of enzyme
Slide 16
More Hormone Action Synergistic effect - activity of two
hormones together greater than either one alone (e.g. estrogen and
LH required for oocyte production) Antagonistic effect - opposite
activity of hormone action (e.g. insulin synthesis of glycogen in
liver, glucagon catabolism of glycogen in liver)
Slide 17
Hormone Secretion Frequently in bursts rather than steady flow
Why? - delayed response, minimizes down-regulation Stimulus for
secretion - neural, sensed changes in blood, other hormones
Homeostatic control mechanisms usually negative feedback systems
But sometimes positive feedback (e.g. oxytocin bringing on
childbirth, LH bringing on ovulation)
Slide 18
Hypothalamus and the Pituitary Pituitary primarily controlled
by hypothalamus - major link between neural and endocrine function
Hypothalamus receives input from limbic system, cortex, thalamus
and RAS, plus visceral sensory and probable visual input
Hypothalamus controls ANS, regulates body temp, thirst, hunger,
sexual behavior and defensive emotions At least 9 hormones from
hypothalamus, 7 from pituitary
Slide 19
Pituitary Anterior and posterior - developmentally different
(ectodermal hypophyseal pouch and neurohyphyseal bud respectively)
Suspended in sella turcica by infundibulum Posterior pituitary
primarily neurosecretory with cell bodies in hypothalamus
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Anterior Pituitary Secrete hormones under control of releasing
or inhibiting hormones of the hypothalamus Hypothalamic hormones
transported via specialized hypophyseal portal system Internal
carotid and communicating arteries supply blood Primary plexus -
capillary bed at base of hypothalamus where neurosecretory cells
release hormones Hypophyseal portal veins Secondary plexus in
anterior pituitary
Slide 21
More Anterior Pituitary Five secretory cell types Somatotrophs
- hGH (somatotropin) - growth and metabolism Thyrotrophs - TSH -
activity of thyroid glands Gonadotrophs - FSH & LH - secretion
of estrogens & progesterones and maturation in ovaries or
secetion of testosterone and sperm production in testes Lactotrophs
- prolactin (PRL) - begins milk production Corticotrophs -
adrenocorticotropic hormone (ACTH) and MSH - secretion of
glucocorticoids in adrenal cortex and skin pigmentation
respectively
Slide 22
Even More Anterior Pituitary Hormones that affect other
endocrine secretions - tropins FSH, LH, TSH, ACTH released by
pituitary Hypothalamic tropins act on pituitary - hypophysiotropic
hormones Ant. pituitary secretion also affected by negative
feedback from target organs
Slide 23
Human Growth Hormone (hGH) Controls growth and metabolism of
cells Stimulates protein synthesis, inhibits protein catabolism -
results in skeletal and muscle growth, tissue repair Alters
molecular energy source by stimulating lypolysis (triglycerides)
and reducing use of glucose for energy production - important for
periods of starvation Glucose in short supply used by neurons May
stimulate glucose to be released by liver cells - insulin
antagonist Excessive secretion can be diabetogenic (beta cell
burnout)
Slide 24
More hGH Increases secretion of insulin-like growth factors
(IGF) from liver, muscle, cartilage, bone, etc. - increases
permeability of cell membrane to amino acids for protein synthesis
associated with growth and division (intimately involved with other
hGH activities) May be carried by blood or act as autocrine or
paracrine Hypothalamic tropin (GHRH or GHIH) release regulated by
blood glucose Low glucose increases GHRH
Slide 25
Even More hGH Other factors that increase secretion Decreased
fatty acids or elevated amino acids in blood Stage 3 & 4 NREM
sleep Increase sympathetic activity Other hormones - glucagon,
estrogens, cortisol, insulin Other factors that decrease secretion
Increased fatty acids or lowered amino acids in blood REM
sleep
Slide 26
Still More hGH Emotional deprivation Obesity Low thyroid
hormones Abnormal secretory levels Pituitary dwarfism - low during
childhood Gigantism - high during childhood Acromegaly (thickened
bones in hands, feet and face, enlarged facial features, thickened
skin) - high during adulthood
Slide 27
Thyroid Stimulating Hormone (TSH) Also thyrotropin Stimulates
secretion of triiodothyronine (T 3 ) and thyroxine (T 4 ) by
thryroid gland Secretion controlled by thyrotropin releasing
hormone (TRH) from hypothalamus based on TSH, T 3, blood glucose
level and metabolic rate
Slide 28
Follicle Stimulating Hormone (FSH) In females - stimulates
ovarian follicular growth on monthly basis and follicular cells to
secrete estrogen In males - stimulates sperm production Secretion
controlled by gonadotropin releasing hormone (GnRH) from
hypothalamus based on blood estrogen or testosterone levels
Slide 29
Luteinizing Hormone (LH) In females - stimulates follicular
cells to secrete estrogen, initiates ovulation, formation of corpus
luteum in ovary (after ovulation) and corpus luteal release of
progesterone Both estrogen and progesterone important in
development of uterine lining for implantation of egg and
preparation of mammary glands for milk secretion
Slide 30
More LH In males - stimulates testicular interstitial cell
development and release of testosterone Secretion controlled by
GnRH
Slide 31
Prolactin (PRL) Initiates and maintains milk production Effect
of prolactin only after preparation of mammary glands by other
hormones (estrogen, progesterone, glucocorticoids, hGH, thyroxine
and insulin)
Slide 32
More Prolactin Secretion controlled by prolactin inhibiting
hormone (PIH, dopamine) from hypothalamus based on estrogen and
progesterone levels Declining estrogen and progesterone levels as
menstruation begins and infant suckling activity retards secretion
of PIH Secretion also controlled by prolactin releasing hormone
(PRH) from hypothalamus during pregnancy
Slide 33
Adrenocoticotropic Hormone (ACTH) Also adrenocorticotropin
Precursor to ACTH (and MSH) is pro- opiomelanocortin (POMC)
produced by corticotrophs; subsequently fragmented to ACTH (and
MSH) Controls production and release of glucocorticoids by adrenal
cortex
Slide 34
More ACTH Secretion controlled by corticotropin releasing
hormone (CRH) from hypothalamus based on glucocorticoids levels And
also low blood glucose, physical trauma, and interleukin produced
by macrophages
Slide 35
Melanocyte-Stimulating Hormone (MSH) Darkens skin through
melanocyte activity Secretion enhanced by CRH and inhibited by
dopamine from hypothalamus
Slide 36
Posterior Pituitary Gland Site of storage (in nerve terminals)
and release of oxytocin (OT) and antidiuretic hormone (ADH or
vasopressin) Secretory neurons descend from hypothalamic nuclei via
supraopticohypophyseal tract Blood flow - inferior hypophyseal
arteries plexus of the infundibular process posterior hypophyseal
veins
Slide 37
Oxytocin (OT) Increases contraction of smooth muscle in uterine
wall during childbirth in response to stretching of cervix -
positive feedback Increases contraction of smooth muscle around
mammary gland cells postpartum causing ejection of milk in response
to nipple stimulation (which also enhances prolactin release) Both
are examples of neuroendocrine reflex Importance unclear at other
times and in males
Slide 38
Antidiuretic Hormone (ADH) Conserves water by increasing kidney
reabsorption and reduced sweating Without ADH, kidneys would
produce 20 liters of urine/day instead of 1-2 Increases blood
pressure by smooth muscle vasoconstriction in blood vessels when
blood volume has declined Secretion controlled by activity of
osmoreceptors in hypothalamus
Slide 39
More ADH Secretion affected by other stimuli - pain, stress,
nicotine, various drugs and alcohol Alcohol inhibits ADH secretion
causing dehydration Diabetes insipidus with symptoms of
substantial, dilute urine production Neurogenic (reduced secretion)
vs. nephrogenic (reduced kidney response to ADH)
Slide 40
Thyroid Lateral lobe and isthmus with substantial blood supply
via branches of internal carotid arteries and jugular veins
Ultrastructure - thyroid follicle with follicular and
parafollicular cells (C cells) Follicular cells produce thyroxine
(tetraiodothyronine or T 4 ) and triiodothyronine (T 3 ),
parafollicular cells produce calcitonin Thyroid only gland to store
substantial quantities of hormones (100 days)
Slide 41
Production of T 3 and T 4 From blood - active transport of
iodide (20-40 times greater) Within follicular cells - production
of precursor - thyroglobulin (TGB) and oxidation of iodide to
iodine Follicular lumen (storage site) - iodination of tyrosine
portion of TGB with 1 or 2 iodine (T 1 or T 2 ) and coupling to
form T 3 and T 4 (1:4 ratio)
Slide 42
More Production of T 3 and T 4 Within follicular cells -
lysosome digestion of TGB to cleave off T 3 & T 4, remnants
recycled T3 more active than T4 Secretion via lipid soluble
diffusion into blood and transported in blood by thyroxine-binding
globulin (TBG) Upon entering target cell, T 4 frequently converted
to T 3
Slide 43
T 3 and T 4 Action Increase BMR (use of O 2 ) via increase
production of Na + /K + ATPase for electrogenic pump, heat
increases body temperature Increased cellular metabolism via
increased protein synthesis, increased use of glucose as ATP
source, increased lipolysis (including elevated cholesterol in bile
which enhances lipid digestion)
Slide 44
More T 3 and T 4 Action Regulates growth and development (in
addition to hGH & insulin), particularly the nervous &
reproductive system Up-regulates receptors of catecholamines (epi
& norepi) Secretion controlled by hypothalamus based on low
metabolic rate or low levels of T 3 or T 4 in blood Check effects
of hypo- or hypersecretion
Slide 45
Calcitonin (CT) Produced by parafollicular cells Lowers blood
calcium and phosphates by decreasing activity of osteoclasts Loss
of calcitonin production has little effect - reason unknown
Slide 46
Parathyroid Glands Bilateral superior and inferior parathyroid
glands attached to thyroid Composed of two cell types - principal
and oxyphil cells Principal cells produce parathyroid hormone (PTH)
Function of oxyphil cells unknown
Slide 47
Parathyroid Hormone (PTH) Increases bone reabsorption (and
calcium and phosphate in blood) via increased osteoclasts and their
activity Increases kidney reabsorption of Ca 2+ and Mg 2+ Inhibits
kidney phosphate (HPO 4 2- ) reabsorption - effect ultimately
lowers phosphate level in blood
Slide 48
More Parathyroid Hormone Stimulates kidney manufacture of
calcitriol from Vit. D which enhances Ca 2+, HPO 4 2-, and Mg 2+
absorption by digestive tract Secretion controlled by Ca 2+ level
in blood
Slide 49
Adrenal Cortex Adrenal gland structurally and functionally
divided into cortex and medulla Develops from mesoderm Cortex
consists of three layers, each secreting different hormones Outer
layer - zona glomerulosa produces mineralocorticoids that control
mineral homeostasis Middle layer - zona fasiculata produces
glucocorticoids Inner layer - zona reticularis produces androgens
(male sex hormones)
Slide 50
Mineralocorticoids Primarily (95%) aldosterone Increases kidney
tubular reabsorption of Na + which secondarily increases
reabsorption of Cl - and HCO 3 - and water retention Increases
kidney excretion of K + and H + Secretion controlled by renin-
angiotensin pathway based on dehydration, low Na + or
hemorrhage
Slide 51
Glucocorticoids Primarily (95%) cortisol (hydrocortisone)
Increases protein catabolism primarily in muscle Stimulates
gluconeogenesis in liver from amino acids or lactic acid Stimulates
lypolysis in adipose cells Provides an anti-inflammatory effect by
reducing # of mast cells that produce histamine, decrease lysosomal
release of enzymes, lower permeability of capillaries and retard
phagocytosis
Slide 52
More Glucocorticoids Depress immune response (decreases tissue
rejection in transplant cases) Secretion controlled by hypothalamus
(corticotropin releasing hormone (CRH)) based on cortisol level in
blood Increased release in response to stress, increasing
availability of ATP and heightened response to vasoconstrictors
Hyposecretion - Addisons disease Hypersecretion - Cushings
syndrome
Slide 53
Androgens Primarily dehyroepiandrosterone (DEHA) Androgen
secretion appears more significant in females (sex drive and
behavior), post-menopausal estrogen source (converted) and in
prepubertal growth and pubertal maturation in both sexes Secretion
probably controlled by ACTH In males, largest proportion of
androgens from testes
Slide 54
Adrenal Medulla Develops from ectoderm Composed primarily of
chromaffin cells which are innervated by preganglionic neurons of
sympathetic NS (thus chromaffin cells are specialized
postganglionic cells) Neurotransmitter epi (80%) and norepi
Increases blood pressure (increased HR, force of contraction,
vasoconstriction)
Slide 55
More Adrenal Medulla Dilate air passages to lungs Decrease
digestion, increase blood glucose, and stimulate metabolism Secrete
based on neural input from hypothalamus
Slide 56
Pancreas Both exocrine (structurally as acini, digestive
function) and endocrine function About 1% of cells are pacreatic
islets (islets of Langerhans) Four different hormone secreting cell
types Alpha (A) cells (20%) - glucagon Increases blood glucose Beta
(B) cells (70%) - insulin Decreases blood glucose
Slide 57
More Pancreas Delta (D) cells (5%) - somatostatin (same as
GHIH) Inhibits release of insulin & glucagon (paracrine
activity on alpha & beta cells), and retards nutrient
absorption in GI tract F cells - pancreatic peptide Inhibits
release of somatostatin, gallbladder contraction, and pancreatic
digestive enzymes Antagonistic control of blood glucose by glucagon
and insulin Diabetes mellitus - review causes and symptoms for Type
I & II
Slide 58
Many Other Hormones Ovaries - estrogens, progesterone, inhibin,
relaxin Testes - testosterone, inhibin Pineal gland - melatonin
Thymus - thymosin, thymic humoral factor (THF), thymic factor,
thymopoietin Eicosanoid secretors A variety of growth factor
sources
Slide 59
Hormones & Stress Homeostatic control vs. response to
prolonged or extreme stress (general adaptation syndrome - GAS) GAS
results in resetting of normal control conditions Alarm reaction -
sympathetic action Resistance reaction - hypothalamus/anterior
pituitary action